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Journal of natural products
American Society of Pharmacognosy
Journal of natural products

American Society of Pharmacognosy

0163-3864

Journal of natural products/Journal Journal of natural productsSCICCR
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    Halimane Diterpenes in the Alpine Daisy Celmisia viscosa: Absolute Configuration, 2,6-Dideoxyhexopyran-3-ulosides, Conformational Flexibility, and Intraspecific Variation

    Richards David J.Lucas Nigel T.Garden Anna L.Saldivia Pe?rez Patricio R....
    11页
    查看更多>>摘要：The methyl-migrated bicyclic skeleton of the halimane diterpenes has been found in a wide range of organisms, including flowering plants, liverworts, marine animals, and bacteria. The discovery of halima-1(10),14-dien-13-ol (3) from the Aotearoa New Zealand endemic alpine daisy Celmisia viscosa is now reported. The full configuration was assigned for the first time by X-ray crystallography, enantiomeric to that of a liverwort isolate. The absolute configuration at C-5 of the halimane is opposite to that at C-5 of the labdane epimanool (1) found in some C. viscosa specimens. Two new 2,6-dideoxyhexopyran-3-uloside halimane derivatives (4 and 5) were also found, and the absolute configuration of 5 was determined by 1H NMR analysis of the Mosher esters. Line broadening in the 13C NMR spectra of these halim-1(10)-enes was due to conformational exchange in the decalin ring A, as shown by molecular modeling and DFT calculations. 1H NMR and GC analyses of leaf extracts of individual plants from across the full geographic range of C. viscosa revealed intraspecific variation of diterpenes: 37 samples had halimadienol as the main diterpene in large amounts and 2 specimens had predominantly epimanool, again in large amounts. Three other viscid (sticky leaved) Celmisia species also contained diterpenes, but none was detectable in four nonviscid Celmisia species.
      原文链接:
    • NSTL
    • Amer Chemical Soc

    O?Acylated Flavones in the Alpine Daisy Celmisia viscosa: Intraspecific Variation

    Rubin DavidSansom Catherine E.Lucas Nigel T.McAdam C. John...
    8页
    查看更多>>摘要：Flavonoids acylated on their core phenolic groups are rare. The Aotearoa New Zealand endemic alpine daisy Celmisia viscosa is widespread, but its flavonoids have not previously been identified. Leaf extracts yielded a series of 8-O-acylated flavones with combinations of 3-methylbutanoate, 2-methylbutanoate, and 2-methylpropanoate groups and one, two, or three O-methyls, all previously unreported. Regiochemistries of 8-(3″-methylbutanoyl)-5-hydroxy-6,7,4′-trimethoxyflavone (5) and 8-(2″-methylbutanoyl)-5,7,4′-trihydroxy-6-methoxyflavone (10) were defined by X-ray crystallography. LC analyses of leaf extracts from the full geographic range of C. viscosa showed intraspecific variation of these flavones: most had high concentrations of trimethoxy 8-O-acylated flavones, but dimethoxy 8-O-acylated flavones were the most abundant flavonoids in two individuals. Three other viscid (sticky leaved) Celmisa species also contained these rare flavones, but four nonviscid Celmisa had none detectable.
      原文链接:
    • NSTL
    • Amer Chemical Soc

    Reconsideration of the Structures of Stemara-13(14)-en-18-ol and Related Diterpene Natural Products: Vinylic Hydrogen Chemical Shifts Are Key

    Tantillo Dean J.Merrill Amy T.
    6页
    查看更多>>摘要：The reported synthesis of stemara-13(14)-en-18-ol, which revealed that the structure of this natural product was misassigned, prompted an investigation using density functional theory methods into the structural reassignment of this natural product and related diterpenoids extracted from Calceolaria plants. 1H and 13C chemical shift predictions led to the reassignment of relative configuration, and in one case the carbon skeleton, of several diterpenoids from Calceolaria. In many of these cases, the chemical shift of the vinylic hydrogen was found to be diagnostic.
      原文链接:
    • NSTL
    • Amer Chemical Soc

    Moroidin, a Cyclopeptide from the Seeds of Celosia cristata That Induces Apoptosis in A549 Human Lung Cancer Cells

    Xu XiaoyaJiang NanLiu ShangmingJin Yang...
    10页
    查看更多>>摘要：Interference of microtubule dynamics with tubulin-targeted drugs is a validated approach for cancer chemotherapy. Moroidin (1) is an Urticaceae-type cyclopeptide having a potent inhibitory effect on purified tubulin polymerization. So far, moroidin has not been chemically synthesized, and its effect on cancer cells remains unknown. Herein, the cyclopeptide moroidin was isolated and identified from the seeds of Celosia cristata, and a revised assignment of its NMR data was presented. For the first time, moroidin (1) was demonstrated as having cytotoxic effects for several cancer cells, especially A549 lung cancer cells. The cellular evidence obtained showed that moroidin disrupts microtubule polymerization and decreases β-tubulin protein levels, but is not as potent as colchicine. Molecular docking indicated that 1 has a high binding potential to the vinca alkaloid site on tubulin. Moreover, moroidin arrested A549 cells in the G2/M phase and induced cell apoptosis. The intrinsic mitochondrial pathway and AKT were involved in the moroidin-induced cell apoptosis. In addition, moroidin (1) inhibited the migration and invasion of A549 cells at sublethal concentrations.
      原文链接:
    • NSTL
    • Amer Chemical Soc

    Micrococcin P2 Targets Clostridioides difficile

    Son Young-JinKim Young-RokOh Sang-HunJung Sungji...
    8页
    查看更多>>摘要：Clostridioides difficile infection is a global public health threat. Extensive in vitro assays using clinical isolates have identified micrococcin P2 (MP2, 1) as a particularly effective anti-C. difficile agent. MP2 possesses a mode of action that differs from other antibiotics and pharmacokinetic properties that render it especially promising. Its time–kill studies have been investigated using hypervirulent C. difficile ribotype 027. DSS (dextran sulfate sodium)-induced in vivo mouse studies with that strain indicate that 1 is better than vancomycin and fidaxomicin. Thus, micrococcin P2 is a valuable platform to be exploited for the development of new anti-C. difficile antibiotics.
      原文链接:
    • NSTL
    • Amer Chemical Soc

    Tamarixetin Attenuated the Virulence of Staphylococcus aureus by Directly Targeting Caseinolytic Protease P

    Kong XiangriHou JuanWang LiWei Lin...
    9页
    查看更多>>摘要：Staphylococcus aureus, especially drug-resistant S. aureus infections, is a worldwide healthcare challenge. There is a growing focus on antivirulence therapy against S. aureus. Caseinolytic protease p (ClpP) is a protein hydrolase essential for pathogenicity in S. aureus. A flavonoid compound, tamarixetin, which was screened in this work, was specifically able to inhibit the hydrolytic activity of ClpP on the fluorescent substrate Suc-LY-AMC with an IC50 of 49.73 μM, without affecting the growth of methicillin-resistant S. aureus strain USA300 and was without obvious cytotoxicity. Further assays found that tamarixetin inhibited the transcription of hla, agr, RNAIII, pvl, PSM-α, and spa genes as well as suppressed the protein expression levels of Hla and PVL. Moreover, tamarixetin was observed to dramatically inhibit the hemolytic activity of hla in S. aureus. Consistent with that of S. aureus USA300-ΔclpP, tamarixetin was shown to increase urease expression. The thermal shift and cellular thermal shift assays showed that tamarixetin markedly changed the thermal stability of ClpP. The dissociation constant (K D) value of tamarixetin with ClpP was 2.52 × 10–6 M measured by surface plasmon resonance. The molecular docking and ClpP point mutation results also demonstrated that tamarixetin had a strong interaction with ClpP. In vivo study showed that tamarixetin was effective in protecting mice from S. aureus pneumonia by increasing survival, reducing lung tissue load, and slowing down the infiltration of inflammatory factors. In addition, tamarixetin was able to enhance the antibacterial activity of cefotaxime in combination. In conclusion, tamarixetin was promising as a ClpP inhibitor for S. aureus infections.
      原文链接:
    • NSTL
    • Amer Chemical Soc

    Synthesis and Biological Evaluation of Steviol Derivatives with Improved Cytotoxic Activity and Selectivity

    Liu Jian-SongXu GengXu Xiao-JiaXu Chao...
    14页
    查看更多>>摘要：Steviol is an ent-kaurene diterpenoid with interesting pharmacological activity. Several steviol derivatives with an exo-methylene cyclopentanone unit were discovered as potent antitumor agents. However, their poor selectivity for tumor cells relative to normal cells reduces their prospects as potential anticancer drugs. In this study, based on previous work, 32 steviol derivatives, including 28 new analogues, were synthesized. Their cytotoxicity against tumor cells and normal cells was evaluated. Several new derivatives, such as 7a, 7h, and 8f, with improved cytotoxic selectivity and antiproliferative activity were obtained, and the structure–activity relationship correlations were investigated. The new compound 8f displayed potent antiproliferative activity against Huh7 cells (IC50 = 2.6 μM) and very weak cytotoxicity against the corresponding normal cells HHL5 (IC50 = 97.0 μM). Further investigation showed that 8f arrested the cell cycle at the G0/G1 phase and caused reactive oxygen species overproduction, decreased mitochondrial membrane potential, and induced apoptosis of Huh7 cells through inhibition of the PI3K/Akt/mTOR and NF-κB pathway as well as upregulation of Bax/Bcl-2 ratio. The present study suggested that 8f is a promising lead compound for new cancer therapies, and the results presented herein may encourage the further modification of steviol for additional derivatives with enhanced efficacy and selectivity.
      原文链接:
    • NSTL
    • Amer Chemical Soc

    Cryptic Epoxytiglianes from the Kernels of the Blushwood Tree (Fontainea picrosperma)

    Chianese GiuseppinaAmin Hawraz Ibrahim M.Maioli ChiaraReddell Paul...
    8页
    查看更多>>摘要：The kernels of the Australian blushwood tree (Fontainea picrosperma) are the source of the veterinary anticancer drug tigilanol tiglate (2a, Stelfonta) and contain a concentration of phorboids significantly higher than croton oil, the only abundant source of these compounds previously known. The oily matrix of the blushwood kernels is composed of free fatty acids and not by glycerides as found in croton oil. By active partitioning, it was therefore possible to recover and characterize for the first time a cryptic tigliane fraction, that is, the diterpenoid fraction that, because of its lipophilicity, could not be obtained by solvent partition of crude extracts. The cryptic tigliane fraction accounted for ca. 30% of the tigliane kernel titer and was quantified by 1H NMR spectroscopy and profiled by HPLC-MS. Long-chain (linoleates and/or oleates) 20-acyl derivatives of the epoxytigliane diesters tigilanol tiglate (EBC-46, 2a), EBC-47 (4a), EBC-59 (5a), EBC-83 (6a), and EBC-177 (7a) were identified. By chemoselective acylation of EBC-46 (2a) and EBC-177 (7a) the natural triesters 2b and 7b and a selection of analogues were prepared to assist identification of the natural compounds. The presence of a free C-20 hydroxy group is a critical requirement for PKC activation by phorbol esters. The unexpected activity of 20-linoleoyl triester 2b in a cytotoxicity assay based on PKC activation was found to be related mainly to its hydrolysis to tigilanol tiglate (2a) under the prolonged conditions of the assay, while other esters were inactive. Significant differences between the esterification profile of the epoxytigliane di- and triesters exist in F. picrosperma, suggesting a precise, yet elusive, blueprint of acyl decoration for the tigliane polyol 5-hydroxyepoxyphorbol.
      原文链接:
    • NSTL
    • Amer Chemical Soc

    Neocucurbols A–H, Phomactin Diterpene Derivatives from the Marine-Derived Fungus Neocucurbitaria unguis-hominis FS685

    Hu JinhuaZou ZhenxingChen YuchanLi Saini...
    9页
    查看更多>>摘要：Neocucurbols A–D (1–4) are diterpene derivatives that possess a complex 6/6/5/5/6 polycyclic ring system with a characteristic tetrahedrofuran bridge ring skeleton. Neocucurbols E–H (5–8) are diterpenes that feature a 6/8/6 tricyclic ring system. Their structures were unambiguously determined by detailed spectroscopic analyses, X-ray diffractions studies, and ECD calculations. All compounds (1–8) were evaluated for in vitro antimicrobial and cytotoxic activities.
      原文链接:
    • NSTL
    • Amer Chemical Soc

    Noncanonical Strigolactone Analogues Highlight Selectivity for Stimulating Germination in Two Phelipanche ramosa Populations

    Taulera QuentinAndna LucileMiesch LaurenceRochange Soizic...
    17页
    查看更多>>摘要：Strigolactones (SLs) are plant hormones exuded in the rhizosphere with a signaling role for the development of arbuscular mycorrhizal (AM) fungi and as stimulants of seed germination of the parasitic weeds Orobanche, Phelipanche, and Striga, the most threatening weeds of major crops worldwide. Phelipanche ramosa is present mainly on rape, hemp, and tobacco in France. P. ramosa 2a preferentially attacks hemp, while P. ramosa 1 attacks rapeseed. The recently isolated cannalactone (14) from hemp root exudates has been characterized as a noncanonical SL that selectively stimulates the germination of P. ramosa 2a seeds in comparison with P. ramosa 1. In the present work, (?)-solanacol (5), a canonical orobanchol-type SL exuded by tobacco and tomato, was established to possess a remarkable selective germination stimulant activity for P. ramosa 2a seeds. Two cannalactone analogues, named (±)-SdL19 and (±)-SdL118, have been synthesized. They have an unsaturated acyclic carbon chain with a tertiary hydroxy group and a methyl or a cyclopropyl group instead of a cyclohexane A-ring, respectively. (±)-SdL analogues are able to selectively stimulate P. ramosa 2a, revealing that these minimal structural elements are key for this selective bioactivity. In addition, (±)-SdL19 is able to inhibit shoot branching in Pisum sativum and Arabidopsis thaliana and induces hyphal branching in the AM fungus Rhizophagus irregularis, like SLs.
      原文链接:
    • NSTL
    • Amer Chemical Soc